155 research outputs found
Lincoln Heights, Chatham County : a community diagnosis including secondary data analysis and qualitative data collection
This document is a result of a community diagnosis of Lincoln Heights, a community in Siler City, North Carolina. The diagnosis was completed by four graduate students from the Department of Health Behavior and Health Education, School of Public Health, The University of North Carolina at Chapel Hill. Community diagnosis is a process to understand what it is like to live in a given community. The process involves examining the culture and functioning of a community, exploring its strengths and assets, and discovering issues of concern to the community members. To gain a better understanding of Lincoln Heights, the first part of the project involved gathering census data for the community, county, and state. Secondary data was collected on the neighborhood's economics, history, environment, housing, education, health concerns, and other social issues, and then compared to county and state figures. There were limitations to these methods of data collection. Wherever possible, data was collected on a community or town level. However, most of the health and community profile data was available only on a county-wide basis or by block group and may not be representative of the Lincoln Heights community, a very small neighborhood within the county. Data that is representative of Chatham County, and not necessarily Lincoln Heights, is so identified in the community profile and health sections of the document. Limitations to collecting secondary data included a lack of current information, especially with regard to immigration statistics and demographic characteristics. Another problem encountered was the lack of identification of statistics for Latinos within the specified census race categories, resulting in difficulty in distinguishing various racial indicators. To obtain a more accurate picture of the community, the second portion of the project focused on a qualitative assessment of community members' opinions on the quality of life in Lincoln Heights. Interviews contained personal background questions as well as questions about life in the Lincoln Heights community. Questions were asked about the strengths and weaknesses of the community to determine what issues could be addressed in the future. Service provider questions focused on the type of services provided as well as the provider’s perspective on the competence of the Lincoln Heights community. The interview process was approved by the University of North Carolina School of Public Health Institutional Review Board (IRB), which must approve all requests from School of Public Health students or faculty to conduct research on human subjects. Interviews began in November 1997 and concluded in January 1998. Members of the community diagnosis team interviewed 23 community members and eight service providers. In addition, 46 community members completed short surveys on two separate occasions, and two focus groups were held in the community. Interviews focused primarily on the strengths of the community, as well as issues of concern, including housing, recreation, substance abuse, and the growth of the Latino population in the neighborhood. The community diagnosis process concluded in February with a community forum. A comprehensive report on the Forum is included in Appendix E of this document. Limitations in the qualitative data collection process included time constraints imposed by the IRB process. The “snowball” sampling process of obtaining referrals yielded a homogeneous group, and difficulties in gaining entree to other, less accessible, community members. These two things were a barrier to gaining the perspective of a more representative sample. Finally, building the trust necessary to gain full disclosure about sensitive issues in a community is a long, ongoing process and takes more time than the community diagnosis process allows. This document was produced to present back to the community the comprehensive findings of the team about the Lincoln Heights community. The first half of the document includes sections representing our secondary data collection and analysis. Chapters include: Geography, History, Economic Outlook, Community Profile, and Health. The second half contains a review of qualitative data collected from interviews and is divided into chapters representing the salient issues facing the community, including: Community Assets and Resources, Education, Politics and Government, Immigration, Crime and Safety, Drugs, Housing, Recreation, and A Changing Climate. During the interview process, community members shared with us many of their views, experiences, and concerns about life in Lincoln Heights. Some of the strengths and challenges that were identified as most important to the community are: Commitment to Community: Members of the community are very active in the community and committed to Lincoln Heights. They also belong to, and take pride in, several strong local associations and organizations. Their affiliation with church and religious organizations is an important part of their lives. Family Ties: The Lincoln Heights neighborhood has an extensive history, with multiple generation families still living there. There are bonds and family ties that run deep in the community. Community Involvement: The strengths of commitment and roots in Lincoln Heights have led to several successful endeavors and achievements. Growth of Latino Population: Over the past several years, the size of the Latino population has grown significantly in Lincoln Heights. This growth has impacted community resources, schools, and community services, as well as introduced difficulties in communication due to a language barrier. Housing: The community continues to experience a shortage of affordable housing and expressed concerns about the condition of some of the homes and trailers in the neighborhood. Youth Recreation: Community members expressed concerns about a lack of recreation for the youth of the neighborhood. Crime and Drugs: Substance abuse was also indicated as a problem, both with the use and sale of illegal drugs occurring within the neighborhood. Future Directions and Conclusions Although numerous issues still exist in Lincoln Heights, much has changed since the last community diagnosis was completed there in 1994. Concerned citizens from the neighborhood have worked hard to build a healthier community and throughout this document we have tried to highlight their successes. Two organizations in particular have impacted the quality of life for residents, the Lincoln Heights Improvement Association and the Chatham Alumni Advancement Association. As was mentioned previously, the Lincoln Heights Improvement Association has played a vital role in the neighborhood by building Washington Park and also by demonstrating that a small group of concerned residents could affect change. The Chatham Alumni Advancement Association also showed that strength in numbers could work when they pressured the local government to give them part of the old Chatham Middle School for use as a cultural center. Both of these groups have proved themselves capable of taking on the issues that face the neighborhood, and winning. It is our hope that these groups will continue to thrive and that they will be able to use this document to steer their course of action in the future.Master of Public Healt
Breast cancer biologic and etiologic heterogeneity by young age and menopausal status in the Carolina Breast Cancer Study: a case-control study
Abstract Background Young-onset breast cancer (<40 years) is associated with worse prognosis and higher mortality. Breast cancer risk factors may contribute to distinct tumor biology and distinct age at onset, but understanding of these relationships has been hampered by limited representation of young women in epidemiologic studies and may be confounded by menopausal status. Methods We examined tumor characteristics and epidemiologic risk factors associated with premenopausal women’s and young women’s breast cancer in phases I–III of the Carolina Breast Cancer Study (5309 cases, 2022 control subjects). Unconditional logistic regression was used to assess heterogeneity by age (<40 vs. ≥40 years) and menopausal status. Results In both premenopausal and postmenopausal strata, younger women had more aggressive disease, including higher stage, hormone receptor-negative, disease as well as increased frequency of basal-like subtypes, lymph node positivity, and larger tumors. Higher waist-to-hip ratio was associated with reduced breast cancer risk among young women but with elevated risk among older women. Parity was associated with increased risk among young women and reduced risk among older women, while breastfeeding was more strongly protective for young women. Longer time since last birth was protective for older women but not for young women. In comparison, when we stratified by age, menopausal status was not associated with distinct risk factor or tumor characteristic profiles, except for progesterone receptor status, which was more commonly positive among premenopausal women. Conclusions Age is a key predictor of breast cancer biologic and etiologic heterogeneity and may be a stronger determinant of heterogeneity than menopausal status. Young women’s breast cancer appears to be etiologically and biologically distinct from that among older women
Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context
Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts
Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas
This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing
molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin
Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images
Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images
of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL
maps are derived through computational staining using a convolutional neural network trained to
classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and
correlation with overall survival. TIL map structural patterns were grouped using standard
histopathological parameters. These patterns are enriched in particular T cell subpopulations
derived from molecular measures. TIL densities and spatial structure were differentially enriched
among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial
infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic
patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for
the TCGA image archives with insights into the tumor-immune microenvironment
Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial
Background
Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy
Frequency of breast cancer subtypes among African American women in the AMBER consortium
Abstract Background Breast cancer subtype can be classified using standard clinical markers (estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2)), supplemented with additional markers. However, automated biomarker scoring and classification schemes have not been standardized. The aim of this study was to optimize tumor classification using automated methods in order to describe subtype frequency in the African American Breast Cancer Epidemiology and Risk (AMBER) consortium. Methods Using immunohistochemistry (IHC), we quantified the expression of ER, PR, HER2, the proliferation marker Ki67, and two basal-like biomarkers, epidermal growth factor receptor (EGFR) and cytokeratin (CK)5/6, in 1381 invasive breast tumors from African American women. RNA-based (prediction analysis of microarray 50 (PAM50)) subtype, available for 574 (42%) cases, was used to optimize classification. Subtype frequency was calculated, and associations between subtype and tumor characteristics were estimated using logistic regression. Results Relative to ER, PR and HER2 from medical records, central IHC staining and the addition of Ki67 or combined tumor grade improved accuracy for classifying PAM50-based luminal subtypes. Few triple negative cases (< 2%) lacked EGFR and CK5/6 expression, thereby providing little improvement in accuracy for identifying basal-like tumors. Relative to luminal A subtype, all other subtypes had higher combined grade and were larger, and ER-/HER2+ tumors were more often lymph node positive and late stage tumors. The frequency of basal-like tumors was 31%, exceeded only slightly by luminal A tumors (37%). Conclusions Our findings indicate that automated IHC-based classification produces tumor subtype frequencies approximating those from PAM50-based classification and highlight high frequency of basal-like and low frequency of luminal A breast cancer in a large study of African American women
Association of Type 1 Diabetes vs Type 2 Diabetes Diagnosed During Childhood and Adolescence With Complications During Teenage Years and Young Adulthood
The burden and determinants of complications and comorbidities in contemporary youth-onset diabetes are unknown
Identification of six new susceptibility loci for invasive epithelial ovarian cancer.
Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 ] HEALTH ]F2 ]2009 ]223175). The CIMBA data management and data
analysis were supported by Cancer Research.UK grants 12292/A11174 and C1287/A10118. The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research
Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were in part supported by the US National Cancer Institute GAME ]ON Post ]GWAS Initiative (U19 ]CA148112). This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based upon data
generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute (dbGap accession number phs000178.v8.p7). The cBio portal is developed and maintained by the Computational Biology Center at Memorial Sloan ] Kettering Cancer Center. SH is supported by an NHMRC Program Grant to GCT. Details of the funding of individual investigators and studies are provided in the Supplementary Note. This study made use of data generated by the Wellcome Trust Case Control consortium, funding for which was provided by the Wellcome Trust under award 076113. The results published here are, in part, based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancerhttp://dx.doi.org/10.1038/ng.3185This is the Author Accepted Manuscript of 'Identification of six new susceptibility loci for invasive epithelial ovarian cancer' which was published in Nature Genetics 47, 164–171 (2015) © Nature Publishing Group - content may only be used for academic research
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